Journal
CANCER INVESTIGATION
Volume 30, Issue 4, Pages 275-286Publisher
TAYLOR & FRANCIS INC
DOI: 10.3109/07357907.2012.657814
Keywords
Progastrin; p53; Colon cancer; Azoxymethane; Lgr5
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Funding
- NIH [5 R01 DK052778]
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Transgenic mice overexpressing human progastrin (hGAS) show colonic crypt hyper-proliferation and elevated susceptibility to colon carcinogenesis. We aimed to investigate effects of p53 mutation on colon carcinogenesis in hGAS mice. We show that introducing a p53 gene mutation further increases progastrin dependent BrdU labeling and results in markedly elevated number of aberrant crypt foci (ACF) and colonic tumors. We demonstrate that hGAS/Lgr5-GFP mice have higher number of Lgr5+ colonic stem cells per crypt when compared to Lgr5-GFP mice indicating that progastrin changes crypt biology through increased stem cell numbers and additional p53 mutation leads to more aggressive phenotype in this murine colon cancer model.
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